Modulation of functional activity and connectivity by acupuncture in patients with Alzheimer disease as measured by resting-state fMRI

Abstract

Acupuncture has been used in the therapy of Alzheimer disease (AD); however, its neural mechanisms are still unclear. The aim of this study is to examine the effect of acupuncture on the functional connectivity in AD by using resting-state functional magnetic resonance imaging (rs-fMRI). Twenty-eight subjects (14 AD and 14 normal controls) participated in this study. The rs-fMRI data were acquired before and after acupuncture stimulation at the acupoints of Tai chong (Liv3) and Hegu (LI4). During the baseline resting state, by using the amplitude of low-frequency fluctuations (ALFF), we found a significantly decreased or increased ALFF in the AD patients relative to the controls. These regions were located in the right superior frontal gyrus (SFG), left postcentral gyrus, subgenual cingulate cortex (SCC), right middle cingulate cortex (MCC), right inferior frontal gyrus (IFG), right hippocampus and the right inferior temporal gyrus (ITG). Then, we selected these brain regions as seeds to investigate whether regional activity and functional connectivity could be modulated by acupuncture in the AD patients. When compared to the pre-acupuncture stage, several of the above regions showed an increased or decreased ALFF after acupuncture in the AD patients. In addition, the functional connectivity between the hippocampus and the precentral gyrus showed enhancement after acupuncture in the AD patients. Finally, there were close correlations between the functional activity, connectivity and clinical performance in the AD patients. The current study confirmed that acupuncture at Tai chong (Liv3) and He gu (LI4) can modulate functional activity and connectivity of specific cognition-related regions in AD patients.

Fig 1. Protocols for acupuncture.

Fig 2

(A and B). Between-group differences in AD and HC before acupuncture, based on a 2-sample t test with age, gender, education level and mean FDR as covariates. The threshold was set to P < 0.001 with topo FDR corrected. The color scale represents t values. Cold color represents decreased ALFF in AD patients compared to HC. AD, Alzheimer’s disease; HC, healthy control; ALFF, amplitude of low-frequency fluctuations.

Fig 3. ALFF changes between post-acupuncture and pre-acupuncture in the AD patients, using the paired-samples T test analysis.

SCC, subgenual cingulate cortex; MCC, middle cingulate cortex; IFG, inferior frontal gyrus; SFG, superior frontal gyrus; ITG, inferior temporal gyrus; **represents significantly changed ALFF in the AD patients when comparing post acupuncture with pre acupuncture (P<0.05); *represents slightly changed ALFF in the AD patients when comparing post acupuncture with pre acupuncture (P>0.05).

Fig 4. The FC differences between pre-acupuncture and post-acupuncture in AD patients (P<0.001, with topoFDR corrected).

Regions which were significantly changed in ALFF were selected as seeds to perform the seed-based interregional correlation analysis. Increased connectivity between the right hippocampus and the left precentral gyrus was found in the AD patients when comparing post-acupuncture with pre-acupuncture.

Fig 5. Correlations of clinical variables and ALFF values in the AD patients.

MMSE, MoCA scores showed positive correlations with ALFF values of the SCC. Negative correlations were shown between AVLT scores and ALFF values of the hippocampus and the right ITG (P<0.05). ALFF, amplitude of low-frequency fluctuations; AD, Alzheimer’s disease; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment; SCC, subgenual cingulate cortex; AVLT, Auditory verbal learning test; ITG, inferior temporal gyrus.

Fig 6. Correlations of clinical variables and hippocampus connectivity in AD patients.

AVLT scores showed negative correlation with connectivity of the right hippocampus and left precentral gyrus (P<0.05). AD, Alzheimer’s disease; AVLT, Auditory verbal learning test.